Mycobacterium tuberculosis, the causative agent for Tuberculosis (TB), currently infects one third of the world's population in its latent form. In 2011 alone, 8.7 million new cases of TB were detected and 1.4 million deaths were attributed to infection by this pathogenic bacteria. World Health Organization, Global tuberculosis Report 2012. For the U.S. in particular, the danger of TB has been significantly risen recently with the by the rapid increasing prevalence of TB cases amongst HIV infected patients. World Health Organization, UNAIDS, and UNICEF, Global HIV/AIDS response: epidemic update and health sector progress towards universal access: Progress Report 2011.
Current treatment for TB, Directly Observed Therapy, Short Course (DOTS), involves the administration of a four-drug cocktail over a two month time span with continuous two-drug treatments for an additional 2-4 months. Implementing the Stop TB Strategy: a handbook for national tuberculosis, 2008, World Health Organization: Geneva, Switzerland. p. 1-198. Despite increasing global efforts to eradicate TB, the estimated rate of curing TB cases has actually declined in last couple of years. Part of this decline has been an upsurge of cases involving multidrug resistant TB strains, MDR-TB and XDR-TB, as well as the increased difficulty of patients complying the lengthy DOTS regiment.
Unfortunately, M. tuberculosis is not the only pathogenic bacterium that has become resistant to current antibiotics. Increasing incidents of other drug resistant bacterium such as Methicillin-resistant Staphylococcus aureus (MRSA) and Carbapenem-resistant Enterobacteriaceae (CRE) are also on the rise. Perez F. et al., Cleve. Clin J Med, 2013. 80(4):225-33; Scheffler, R. J, et al., Appl Microbiol Biotechnol, 2013. 97(3):969-78. Additionally, the threat of drug-resistant weaponized bacterium such as Bacillus anthracia and Yersinia pestis still persists. Froude, J. W, et al., Antibodies for biodefense. MAbs, 2011. 3(6):517-27.
With the global decreasing effectiveness of current therapeutics against TB, increasing prevalence the multi-drug resistant strains MDR-TB and XDR-TB as well as other pathogenic bacterium, there is a strong need for development of antibiotics targeting novel pharmacological targets within pathogenic bacterium such as M. tuberculosis. 